阿戈美拉汀对创伤后应激障碍SD大鼠行为表现的影响
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摘要
目的探究阿戈美拉汀对创伤后应激障碍(PTSD)SD大鼠行为表现的影响。方法将32只SD雄性大鼠随机分为空白对照组(不给药,不应激)、单纯应激组(不给药,应激)、药物组(给药,应激)及单纯药物组(给药,不应激)4组,每组8只。药物组和单纯药物组在应激后12 h内通过灌胃给予阿戈美拉汀2.6 mg∕(kg·d);空白对照组和单纯应激组通过灌胃给予等量生理盐水,共2周。单纯应激组和药物组给予大鼠单次延长结合足底电击应激刺激。第14天在电击箱中检测大鼠的条件性恐惧反应;第15天给予旷场实验,观察其焦虑状态;第16~21天行Morris水迷宫实验,测试其定位航行力和空间探索力。结果应激后大鼠在电击箱中呆滞时间延长;在旷场实验中穿格和站立次数减少;在Morris水迷宫实验中上台时间延长,穿越平台次数减少。相比单纯应激组,应激后早期给予阿戈美拉汀干预,大鼠呆滞行为、焦虑状态及其在Morris水迷宫中的表现均改善(P <0.05)。结论应激后大鼠警觉性和焦虑性增强,学习记忆功能减退。应激后早期给予阿戈美拉汀干预,能有效减少应激后PTSD模型大鼠恐惧、焦虑表现,并对大鼠的学习记忆能力减退有预防作用。
Objective To investigate the effect of Agomelatine on behavioral manifestations of rats with posttraumatic stress disorder(PTSD). Methods Thirty-two male SD rats were randomly divided into a control group(no drug, no stress, n = 8), an SPS & S group(no drug, single prolonged stress & foot shock stress, n = 8), a drug group(drug and stress, n = 8) and a single drug group(drug, no stress, n = 8). The rats of the drug group and the single drug group were administrated with Agomelatine in a dosage of 2.6 mg/(kg·d) by gavage within 12 h after stress for 2 w, while the control group and the SPS & S group were administrated with the same dose of saline for 2 w. After that the rats in the SPS & S group and the drug group were stimulated with SPS & S, the conditioned fear response was observed on the 14 th d in the electric shock box. On the 15 th d the open-field test was conducted in each group to observe the anxiety behaviors, while from the 16 th d to the 21 st d, the Morris water maze test was done to observe the navigation capability and the space exploration ability of the rats. Results After SPS & S stress, theretention time of the rats in the electric shock box was significantly prolonged while the crossing score and rearing score of the rats decreased significantly in the open-field test, and the Morris water maze test also indicated the escape latency period of the rats increased while the number of crossing platform decreased. Furthermore, compared with the SPS & S group, early intervention of Agomelatine after the stress obviously ameliorated sluggish behavior, anxiety state and performance of the rats in the Morris water maze(P < 0.05). Conclusions After stress, the alertness and anxiety of the rats are sharply increased while the learning and memory functions obviously decrease. However, early intervention of Agomelatine after stress could significantly reduce the fear and anxiety-like behaviors of the rats with PTSD and can also prevent the loss of learning and memory functions in rats.
Objective To investigate the effect of Agomelatine on behavioral manifestations of rats with posttraumatic stress disorder(PTSD). Methods Thirty-two male SD rats were randomly divided into a control group(no drug, no stress, n = 8), an SPS & S group(no drug, single prolonged stress & foot shock stress, n = 8), a drug group(drug and stress, n = 8) and a single drug group(drug, no stress, n = 8). The rats of the drug group and the single drug group were administrated with Agomelatine in a dosage of 2.6 mg/(kg·d) by gavage within 12 h after stress for 2 w, while the control group and the SPS & S group were administrated with the same dose of saline for 2 w. After that the rats in the SPS & S group and the drug group were stimulated with SPS & S, the conditioned fear response was observed on the 14 th d in the electric shock box. On the 15 th d the open-field test was conducted in each group to observe the anxiety behaviors, while from the 16 th d to the 21 st d, the Morris water maze test was done to observe the navigation capability and the space exploration ability of the rats. Results After SPS & S stress, theretention time of the rats in the electric shock box was significantly prolonged while the crossing score and rearing score of the rats decreased significantly in the open-field test, and the Morris water maze test also indicated the escape latency period of the rats increased while the number of crossing platform decreased. Furthermore, compared with the SPS & S group, early intervention of Agomelatine after the stress obviously ameliorated sluggish behavior, anxiety state and performance of the rats in the Morris water maze(P < 0.05). Conclusions After stress, the alertness and anxiety of the rats are sharply increased while the learning and memory functions obviously decrease. However, early intervention of Agomelatine after stress could significantly reduce the fear and anxiety-like behaviors of the rats with PTSD and can also prevent the loss of learning and memory functions in rats.
引文
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[10]蔡思琪,李沅衡,黎嘉,等.鼠类行为学实验方法研究进展[J].医学综述,2018,24(5):916-920.
[11]董原君,张跃奇,胡敏,等.催产素对大鼠创伤后应激障碍的预防作用[J].山东医药,2015,55(41):20-22.
[12]BANASR M,SOUMIER A,HERY M,et al.Agomelatine,a new antidepressant,induces regional changes in hippocampal neurogenesis[J].Biol Psychiatry,2006,59(11):1087-1096.
[13]POMPILI M,SERAFINI G,INNAMORATI M,et al.Agomelatine,a novel intriguing antidepressant option enhancing neuroplasticity:a critical review[J].World Journal of Biological Psychiatry,2013,14(6):412-431.
[14]HAUSCHILDT M,PETERS M J,JELINEK L,et al.Veridical and false memory for scenic material in posttraumatic stress disorder[J].Consciousness Cognition,2012,21(1):80-89.
[15]武海霞,吴志刚,刘红彬,等.Morris水迷宫实验在空间学习记忆研究中的应用[J].神经药理学报,2014,4(5):30-35.
[16]刘小兵,杨仲利,黎燕,等.帕罗西汀对创伤后应激障碍模型大鼠的影响[J].临床精神医学杂志,2011,21(6):365-367.
[2]WEYMANN K B,LIM M M.Sleep disturbances in TBI and PTSDand potential risk of neurodegeneration[J].Current Sleep Medicine Reports,2017,3(3):179-192.
[3]H?JGAARD K,CHRISTIANSEN S L,BOUZINOVA E V,et al.Disturbances of diurnal phase markers,behavior,and clock genes in a rat model of depression;modulatory effects of agomelatine treatment[J].Psychopharmacology,2018,235(3):627.
[4]梁大伟,王悦秋,章斌,等.氘代阿戈美拉汀的合成[J].化学研究,2015(1):44-48.
[5]袁秀玉,董原君,梁霞,等.创伤性应激对大鼠海马BDNF表达的影响[J].山东大学学报(医学版),2016,54(4):37-41.
[6]吴婷婷,屈会化,胡丽娜,等.基于树鼩体表面积的树鼩与人类及其它实验动物等效剂量换算系数的测算[J].中华中医药杂志,2015(1):203-205.
[7]STIDD D A,VOGELSANG K,KRAHL S E,et al.Amygdala deep brain stimulation is superior to paroxetine treatment in a rat model of posttraumatic stress disorder[J].Brain Stimulation,2013,6(6):837-844.
[8]周娇娇,阙建宇,于雯雯,等.Morris水迷宫检测动物学习记忆水平的方法学[J].中国老年学杂志,2017,37(24):6274-6277.
[9]孙树峥,张黎明,姬雅君,等.舍曲林抗创伤后应激障碍效应及其对一氧化氮的影响[J].中国药理学与毒理学杂志,2016,30(4):317-322.
[10]蔡思琪,李沅衡,黎嘉,等.鼠类行为学实验方法研究进展[J].医学综述,2018,24(5):916-920.
[11]董原君,张跃奇,胡敏,等.催产素对大鼠创伤后应激障碍的预防作用[J].山东医药,2015,55(41):20-22.
[12]BANASR M,SOUMIER A,HERY M,et al.Agomelatine,a new antidepressant,induces regional changes in hippocampal neurogenesis[J].Biol Psychiatry,2006,59(11):1087-1096.
[13]POMPILI M,SERAFINI G,INNAMORATI M,et al.Agomelatine,a novel intriguing antidepressant option enhancing neuroplasticity:a critical review[J].World Journal of Biological Psychiatry,2013,14(6):412-431.
[14]HAUSCHILDT M,PETERS M J,JELINEK L,et al.Veridical and false memory for scenic material in posttraumatic stress disorder[J].Consciousness Cognition,2012,21(1):80-89.
[15]武海霞,吴志刚,刘红彬,等.Morris水迷宫实验在空间学习记忆研究中的应用[J].神经药理学报,2014,4(5):30-35.
[16]刘小兵,杨仲利,黎燕,等.帕罗西汀对创伤后应激障碍模型大鼠的影响[J].临床精神医学杂志,2011,21(6):365-367.